pdf英语阅读：全浸英语阅读Alzheimer
pdf英语阅读：全浸英语阅读Alzheimer又一个精简表达▷to be marketed as：to enter the market as♜助读笔记▷grant conditional approval：give an approval on condition that...值得学习的精简表达
全浸阅读=Total Immerse Dynamic eReading=TIDE
选自-2021-0612-TE
Alzheimer's Disease：Faint HopesAmerica’s wary approval of an Alzheimer’s drug offers hope to millionsBut its makers still have work to do to prove it can slow the ADvance of dementia阿尔茨海默病（AD）是一种起病隐匿的进行性发展的神经系统退行性疾病。临床上以记忆障碍/失语/失用/失认/视空间技能损害、执行功能障碍以及人格和行为改变等全面性痴呆表现为特征，病因迄今未明。65岁以前发病者称早老性痴呆；65岁以后发病者称老年性痴呆。
直接阅读纯英文原文请点击下面链接跳转： Alzheimer's Disease：Faint Hopes
P1①②③ 104words
1)NEWS THAT America’s Food and Drug Administration (FDA) has granted conditional approval to a new drug aducanumab to be marketed as Aduhelm for the treatment of Alzheimer’s disease has understandably been greeted as a huge breakthrough. 2)For millions of people with Alzheimer’s a remorselessly degenerative illness leading eventually to utter helplessness—and for those caring for them—it is a ray of hope. 3)But the benefits it will offer remain uncertain and the FDA’s decision is controversial.
♜助读笔记
▷grant conditional approval：give an approval on condition that...
值得学习的精简表达
▷to be marketed as：to enter the market as
又一个精简表达
▷has understandably greeted as
understandably这里的出现已经表明了作者的态度，可以理解，但不甚苟同 这是一种condecencension(纡尊)的用词
▷Remorselessly degenerative illness
Remorseless-without regret or guilt; merciless relentless
Degenerative-deterioration of a tissue or an organ in which its function is diminished or its structure is impaired
▷lead eventually to utter helplessness让人心酸的用词
-utter-complete/absolute
▷remain uncertain-unclear，unconfirmed
▷controversial-contentious，public disagreement
▷a ray of hope-a flicker of light华先生的微光
P1：news about a drug has been greeted
开头是高频的社论文章开篇方式，news that...has been greeted as...
第二句也有一个惯用句型，for people that，....，and for those...，it is a ray of hope.一句话竟清楚了同一件事中不同关联方的状况.
Sum: p1 is about a news an illness two groups one organization
美国食品和药物管理局（FDA），有条件批准了一种新药aducanumab，该药将作为Aduhelm上市，用于治疗老年痴呆症，这一消息，被认为是一个巨大的突破。对于数以百万计的阿尔茨海默病患者来说，这是一种无情的退化性疾病，最终导致彻底的无助，而对于那些照顾他们的人来说，这是一线希望。但它将提供的好处仍然不确定，FDA的决定是有争议的。
P2①②③④ 134words
1)It was 115 years ago that Alois Alzheimer a German psychiatrist conducted the autopsy that helped him identify the disease now known as Alzheimer’s. It is much the most common of the dozens of causes of dementia. 2) It accounts for 60-80% of cases of a debilitating condition that affects an estimated 50m people around the world and—as the risk of dementia increases with age and the world is getting older—is spreading fast. 3)The costs in human misery are incalculable. 4)In terms of expenditure in caring for people with the condition they are estimated at over $1trn now and forecast to reach $2trn by 2030.
♜助读笔记
▷conducted the autopsy
Autopsy-post mortem examination check bodies after people death
▷It is much ｛the most common of the dozens of causes of dementia.｝
好多叠加修饰连珠炮，可以学习
▷dementia-mental illness marked by memory disorder persona changes and impaired reasoning
▷A debilitating condition
Debilitate:weaken (of illness) making people very weak and inform
▷The costs in human misery are incalculable.
misery-unhappiness/affliction
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
经115年前，德国精神病学家阿洛伊斯·阿尔茨海默，通过尸检确定了现在被称为阿尔茨海默氏症的疾病。它是导致痴呆症的几十个原因中最常见的。据估计，全球约有5000万人患有老年痴呆症，随着年龄的增长，老年痴呆症的风险也在增加，世界老龄化也在迅速蔓延。人类苦难的代价是无法估量的。就照顾病人的开支而言，目前估计超过1万亿美元，预计到2030年将达到2万亿美元。
P3①②③④126words
1)So even if few have hoped for an imminent cure there is huge pent-up demand for a treatment that at least slows the advance of Alzheimer’s. 2)The FDA claims in its press release on the approval sought by Biogen a biotechnology firm based in Cambridge Massachusetts: “Aduhelm is the first treatment directed at the underlying pathophysiology of Alzheimer’s disease.” 3)In November 2019 China granted conditional approval to Oligomannate (gv-971) a drug produced by Green Valley a company from Shanghai. 4)But Western scientists grumbled the data from the Chinese study were scanty and its conclusions hard to credit.
♜助读笔记
▷imminent cure
Imminent-impending/about to happen
▷A huge pent-up demand For
Pent-up:closely confined or held back/unable to be express or released
#长难句#
▷So even if few have hoped for an imminent cure ｛there is huge pent-up demand for a treatment （that at least slows the advance of Alzheimer’s. ）｝
▷the underlying pathophysiology of Alzheimer’s disease
pathophysiology-the disordered physiology process associated with disease or injury病理
▷grumble-rumble/complaint
▷study were scanty and its conclusions hard to credit.
Scanty-scarce few
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
因此，即使很少有人希望能马上治愈，对至少能延缓老年痴呆症进展的治疗，仍有巨大的需求。美国食品和药物管理局（FDA）在其新闻稿中声称，总部位于马萨诸塞州剑桥的生物技术公司Biogen，正在寻求批准：“Aduhelm是针对阿尔茨海默病潜在病理生理学的第一种治疗方法。”
P4①②③126words
1)So the jubilation in some quarters at Biogen’s coup is understandable. 2)But it is not universal in part because of the tortuous history of the drug’s progress to approval. 3)It is of a type known as a monoclonal antibody—a specialised protein molecule forming part of the immune system—tailored to bind to a protein called beta-amyloid which forms plaques in the brains of people with Alzheimer’s disease and which many researchers have long believed is not just a symptom of Alzheimer’s but at least part of the cause (an idea known as “the amyloid hypothesis”).
♜助读笔记
▷the jubilation in some quarters at Biogen’s coup
-jubilation-a feeling of great happiness exultation
-quarters-districts
-coup:seize of power success
▷Plaques (orange) among brain cells
▷tortuous history of
-tortuous:contour twisted convoluted
▷monoclonal antibody单克隆抗体
當身體有外來的物質（稱為抗原，antigen）侵入時，體內會採取許多防禦措施來破壞或阻擋這些物質，而B細胞所分泌的抗體（antibody）便是其中一種方式。每種抗原分子上通常有許多可誘導出抗體的部分，稱為抗原決定基 (antigenic determinant)，而每個B細胞只能針對一種抗原決定基，產生一種抗體，因此在傳統的血清中，含有許多種不同的抗體，分別對抗不同的抗原決定基。若能挑出各個B細胞，單獨培養成細胞株，則能獲得單一種類的抗體，只會對某一特定抗原決定基反應，則此抗體稱為單株抗體（monoclonal antibody）。
▷forms plaques in brain
神经炎性斑(neurtic plaques NP)在 AD患者的大脑皮质、海马、某些皮质下神经核如杏仁核前脑基底神经核和丘脑存在大量的NP。NP以Aβ沉积为核心 核心周边是更多的Aβ和各种细胞成分。自20世纪70年代以来 相继有研究者制定了诊断AD所需大脑皮质NP数量的神经病理诊断标准 目前广泛使用的是美国学者Mirra等1991年提出的半定量诊断标准 用图像匹配的方法估计三个脑叶新皮质严重受累区NP的数量。
▷#the amyloid hypothesis#
It is of a type known as a monoclonal antibody—a specialised protein molecule forming part of the immune system—tailored to bind to a protein called beta-amyloid which forms plaques in the brains of people with Alzheimer’s disease，and which many researchers have long believed is not just a symptom of Alzheimer’s but at least part of the cause (an idea known as “the amyloid hypothesis”).
阿尔兹海默症（Alzheimer's Disease AD）是最常见的一种以患者的记忆力减退，认知能力障碍，情绪调节异常等为特征的神经退行性疾病。伴随人口寿命的增长，这类严重威胁中老年生命质量的疾病发病率也与日俱增，然而截至目前，对其发病机制的各种解释呈百家争鸣的局势。其中最为普遍被人们接受的是淀粉样蛋白假说（The amyloid hypothesis），淀粉样前体蛋白（amyloid precursor protein APP）作为这一假说的核心，其被β-与γ-分泌酶切割生成的β-淀粉样蛋白（amyloid-β，Aβ）长期以来被认为是导致AD相关病理损伤的始作俑者。因此，从根本上解决Aβ的产生机制问题对于开发针对于AD有效的治疗手段显得尤为重要。
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
p4: the amyloid hyperthesis
因此，一些人对Biogen’s成功之举的欢呼是可以理解的。但它并不具有普遍性，部分原因是，该药获得批准的曲折历史。它属于一种被称为单克隆抗体的类型——一种形成免疫系统一部分的特殊蛋白质分子，专门与一种叫做β-淀粉样蛋白的蛋白质结合，这种蛋白质在阿尔茨海默病患者的大脑中形成斑块，许多研究人员长期以来认为，这不仅仅是阿尔茨海默病的症状，而且至少是部分原因（这个想法被称为“淀粉样蛋白假说”）。
P5①②③107words
1)Aducanumab does indeed seem to reduce the amount of beta-amyloid in the brain. 2)That is why the FDA has approved it. The theory is that this should in turn slow the progress of cognitive degeneration. 3)On that point the evidence is less clear-cut. The FDA approval allows the drug to be used but requires Biogen to carry out a large-scale clinical trial to prove that it does indeed work and warns that if not it could be “pulled from the market”.
♜助读笔记
▷cognitive degeneration
-cognition deterioration turning bad
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
p4: the amyloid hyperthesis
P5: approval for partly function but warns given if not proved more
阿杜单抗，确实能减少大脑中β-淀粉样蛋白的数量。这就是为什么FDA批准了它。理论认为，这反过来会减缓认知退化的进程。在这一点上，证据就不那么明确了。FDA的批准允许使用这种药物，但要求Biogen进行大规模的临床试验，以证明它确实有效，并警告说，如果不行，它可能会“被撤出市场”。
P6①②③④154words
1)Previous efforts to demonstrate its efficacy appeared to have foundered in March 2019 when Biogen and Eisai of Japan announced that they were ending two clinical trials among people with signs of mild cognitive impairment or early-onset Alzheimer’s. Aducanumab had failed a “futility test”—ie the evidence suggested it had no effect. 2)But then in October that year Biogen said a fresh look at the data showed that “patients…experienced significant benefits on measures of cognition and function such as memory orientation and language.” 3)One of the two trials it said showed that higher doses of the drug did have a small but noticeable effect in slowing cognitive decline in people with Alzheimer’s. 4)Biogen said it would seek FDA approval after all.
♜助读笔记
▷demonstrate its efficacy
Efficacy-effectiveness
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
p4: the amyloid hyperthesis
P5: approval for partly function but warns given if not proved more
P6: the tortuous process before approval
此前证明其疗效的努力，似乎在2019年3月宣告失败，当时日本的Biogen和Eisai宣布，他们将结束，对有轻度认知障碍，或早发性阿尔茨海默症症状的人，进行的两项临床试验。. Aducanumab没有通过“无效测试”，也就是说，证据表明它没有效果。但是，在那一年的10月，Biogen说，对数据的重新审视表明，“患者……在认知和功能的测量上，如记忆、取向和语言，体验到了显著的好处。”，研究表明，高剂量的药物确实对减缓老年痴呆症患者的认知能力下降有一个小而显著的效果。Biogen表示，它最终将寻求FDA的批准。
P7①②③④121words
1)A drug prescribed to even a substantial minority of people with dementia would be among the biggest-sellers of all time. 2)The price of Biogen’s shares which had fallen by almost 30% on the day of its announcement that trials had failed bounced back almost as much when it changed its mind and surged again a year later when the FDA made positive comments as well as after its announcement today. 3)Administered intravenously monthly at a clinic aducanumab is likely at first to cost thousands of dollars a year and patients will require constant monitoring as many develop brain oedemas.
♜助读笔记
▷Substantial minority
The smaller number
▷Administered intravenously
into veins静脉注射
▷brain oedemas.脑水肿
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
p4: the amyloid hyperthesis
P5: approval for partly function but warns given if not proved more
P6: the tortuous process before approval
p7: the way and cost to access the drug
一种为少数痴呆症患者开出的药物，将是有史以来最畅销的药物之一。在宣布试验失败的当天，Biogen的股价下跌了近30%，但当它改变主意时，Aducanumab股价反弹了几乎同样多，一年后当FDA发表积极评论时，以及在今天宣布之后，股价再次飙升。在诊所每月静脉注射一次，一开始可能每年花费数千美元，患者需要持续监测，因为许多人会出现脑水肿。
P8①②③④151words
1)Many specialists remain deeply sceptical about aducanumab in particular and the amyloid hypothesis more broadly. 2)Last November ten out of the 11 members of an expert advisory panel appointed by the FDA voted against approving the drug on the basis of the research presented (the 11th was undecided). 3)More recently a new statistical study of various drug trials in Alzheimer’s & Dementia the journal of the Alzheimer’s Association a charity shows what one of its authors Edo Richard a Dutch neurologist calls “overwhelming evidence of absence of an effect of anti-amyloid therapy in general”. 4)Dr Richard finds it “amazing” that the FDA has overruled its own advisory panel to reach the “scientifically questionable” ruling on the drug.
♜助读笔记
▷“overwhelming evidence of absence of an effect of anti-amyloid therapy in general”
Overwhelming-very strong and very large
▷scientifically questionable
都违背科学原则了，非常精炼而又有力的质疑
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
p4: the amyloid hyperthesis
P5: approval for partly function but warns given if not proved more
P6: the tortuous process before approval
p7: the way and cost to access the drug
p8: sceptical voices
P9①②③④⑤151words
1)His paper argues that the time has come to divert therapeutic efforts away from drugs that try to clear beta-amyloid to other lines of investigation. 2)And for all the scepticism about this drug some scientists in the field are optimistic that great progress is being made in combating dementia. 3)Jonathan Schott a professor of neurology at the Dementia Research Centre University College London and chief medical officer of Alzheimer’s Research says that 30-40% of the causes of dementia are modifiable. 4)Already there is evidence that the age-specific incidence of dementia is going down in the West as people live healthier lives: obesity smoking high blood pressure and excessive drinking in middle age are all associated with a higher incidence of dementia. 5)A study published last year in Neurologyfollowed nearly 50 000 people in America and Europe from 1988 to 2015. It found that 8.6% developed dementia. But the risk of being among them had remarkably fallen by an average of about 13% a decade from about a one-in-four chance for a 75-year-old in 1995 to less than one in five.
♜助读笔记
▷#长难句#
His paper argues that ｛the time has come to divert therapeutic efforts away from drugs (that try to clear beta-amyloid) to other lines of investigation.｝
▷Divert away: reroute change the way
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
p4: the amyloid hyperthesis
P5: approval for partly function but warns given if not proved more
P6: the tortuous process before approval
p7: the way and cost to access the drug
p8: sceptical voices
P9: optimistic voices
P10①②③92words
1)Meanwhile great advances have been made in diagnosing dementia. 2)Whereas once this required cognitive tests followed by an expensive brain scan or intrusive lumbar puncture now a simple blood test can predict decades in advance how likely it is that someone will develop Alzheimer’s later in life. 3)Identifying those at risk early means that existing therapies including aducanumab largely ineffective once symptoms are far advanced might be deployed early enough to make a difference.
♜助读笔记
▷Lumbar puncture脊椎穿刺
Lumbar puncture (LP) is a medical procedure in which a needle is inserted into the spinal canal most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. It may also be be done to inject medications into the cerebrospinal fluid particularly for spinal anesthesia or chemotherapy.
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
p4: the amyloid hyperthesis
P5: approval for partly function but warns given if not proved more
P6: the tortuous process before approval
p7: the way and cost to access the drug
p8: sceptical voices
P9: optimistic voices
p10: advances and benefits
P11①②③④⑤⑥⑦⑧164words
1)And other treatments should slowly become available. 2)James Rowe a professor of cognitive neurology at Cambridge believes research into dementia is at a “tipping-point”. 3)He expects the first successes with rare genetic conditions such as Huntington's disease and frontotemporal dementia. 4)Alzheimer’s which may turn out to be an umbrella term for a variety of different contributory pathologies susceptible to different medicines would follow later. 5)Those living with Alzheimer’s have had few reasons for optimism. 6)And Professor Schott argues that the main benefit of the FDA ruling may be that Alzheimer’s will no longer be seen as a “lost cause”. 7)Big pharma and publicly funded researchers will take encouragement. 8)Aducanumab offers a small step forward; bigger ones will come.
♜助读笔记
▷tipping-point: the critical point in a situation process or system beyond which a significant and often unstoppable effect or change takes place有一本书叫《tipping point》讲引爆市场传播
▷Huntington's disease
安徒生童话《红舞鞋》讲述了一双具有魔力的红舞鞋，穿上它就会不自主无休止地跳舞，直到精疲力竭而死去。现实生活中，也有一群会不由自主地做舞蹈动作的人，他们被称为亨廷顿舞蹈症患者。
在现实生活中，有些人会出现挤眉弄眼，口唇挪动，手舞足蹈等症状，就好像在跳着“优美”的舞蹈。实则不然，此“舞蹈”非彼舞蹈，这极有可能是一种致命的“舞蹈”——亨廷顿舞蹈病(Huntington’s disease，简称HD)。亨廷顿舞蹈症是一种神经退行性疾病，由Huntington于1872年首先报道，故而得名
▷frontotemporal dementia
额颞痴呆(frontotemporal dementia)是指中老年患者缓慢出现人格改变言语障碍及行为显示额颞叶萎缩，而病理检查未发现Pick小体及Pick细胞的 [痴呆综合征](包括Pick病及临床表现类似的Pick综合征，后者又包括额叶痴呆和 [原发性进行性失语]，临床以明显的人格、行为改变和认知障碍为特征。
▷turn out to be an umbrella term for a variety of different contributory pathologies susceptible to different medicines
-umbrella term：An umbrella term ora hypernym is a word or phrase used to generally rather than specifically describe a group of varying but identifiably related subjects.
▷susceptible：likely to be affected or influenced
▷Lost cause:a cause with no chance of success
P1：news about a drug has been greeted
P2: the history the damage and the cost of the illness
P3: the market and the expectation
p4: the amyloid hyperthesis
P5: approval for partly function but warns given if not proved more
P6: the tortuous process before approval
p7: the way and cost to access the drug
p8: sceptical voices
P9: optimistic voices
p10: advances and benefits
P11: the significant approval-small step but meaningful
的。
补充阅读：
自2003年后，FDA在2021年6月7日终于又批准了一款对抗阿尔茨海默症的新药Aducanumab（商品名：Aduhelm）。Aduhelm由渤健（Biogen）与卫材（Eisai）联合开发，是一种针对阿尔茨海默症标志性淀粉样蛋白（Aβ）的抗体药物，是第一个阿尔茨海默症的靶向药物。
➤作用机制
Aduhelm是一个人源单克隆IgG1抗体，能透过血脑屏障并选择性地与Aβ聚合物（包括可溶性寡聚物和非可溶性纤维）结合，促进Aβ斑块的清除。
Aduhelm通过抗原-抗体相互作用于阿尔茨海默症标志物Aβ结合
➤临床试验
Aduhelm的临床研究主要由渤健主持。一期临床（NCT01397539， NCT02782975， NCT01677572， NCT02434718， NCT04924140）主要测试了单剂量和多剂量的安全和耐受的剂量范围以及生物利用度。运用PET扫描，研究人员发现Aduhelm组与对照组相比，能有效地减少Aβ斑块。
Aduhelm组Aβ斑块减少：起点和第54周PET示例（NCT01677572 ）
单剂量NCT01397539和NCT02782975分别在2013年8月和2016年11月完成，单剂量和多剂量NCT02434718也在2016年9月完成。但是，多剂量NCT01677572由于三期临床的无效性验证而提前终止。此外，NCT04924140是一个新的研究，用来观察Aduhelm在健康志愿者中的不良反应，预计在2021年7月9日开始，目前还没有开始招募志愿者。
二期临床（NCT03639987）主要探索了在持续给药的情况下对已经没有Aβ成像异常的轻度认知障碍患者的安全性。但是，该二期临床因为三期临床的无效性验证而提前终止了。
三期临床（NCT02477800， NCT02484547， NCT04241068）研究了每月给药的情况下，Aduhelm在延缓认知能力继续下降和功能性损伤的效力以及长期的安全性和耐受性。但是，NCT02477800和NCT02484547因为无效性验证而提前终止了；NCT04241068预计将在2023年10月结束。
➤不良反应
最常见的不良反应为脑水肿和头疼。在像Aduhelm一样与Aβ有关的疗法中，脑水肿与血脑屏障内皮细胞紧密联结瓦解导致的液体聚集有关。
➤结果争议
从上面的临床试验成功与否可以看出，在临床有效性的方面，Aduhelm并没有表现出令人满意的效果。站在新药研发的角度上，只有当一个新药既安全又有效时，才能被考虑获批。
从药企和投资方，到专家和患者群体，药物批准有着众多的利益体，更何况是有望治疗阿尔茨海默症的药物。在反复审阅现有数据、咨询专家组并与患者群体沟通后，面对质疑和期望，FDA最终决定采用“加速批准途径”，为了让患者能够更快的接触到一个可能有效果的药物。目前，Aduhelm定价为56000美元一年，与此同时，渤健和卫材对Aduhelm的临床试验会继续进行。
➤织生科技的看法
时隔18年，阿尔茨海默症新药研发领域终于迎来了一款获批药物。首先，我们必须肯定，这是在人类攻克阿尔茨海默症历史上一个“时代性”的事件。其次，当我们重新看一看Aduhelm临床试验可以发现，Aduhelm临床试验受试者主要为轻度、中度的阿尔茨海默症患者以及轻度认知障碍患者，因此，只有当我们做好早筛查，才能早发现、早干预、早治疗。若不尽早做筛查，等到了晚期的时候，大脑已经不可逆地萎缩，此时，Aduhelm或者其它药物可能也没有作用了。
另外，一年56000美元的价格，对于普通人是一笔巨大的花销。与其面对“有药吃不起”的地步，不如采取“早筛查、早发现、早干预”的行动。通过改善生活习惯，降低认知风险因素、延缓发病时间、降低恶化速度。为此，我们研发出了一个认知筛查小游戏——认知评估游戏，来快速线上筛查，和一个认知症非药物综合干预小程序——脑倍佳 ，帮助中国家庭减少认知症的困扰。研究表明，通过控制认知症相关的风险因素，我们甚至可以降低或延缓40%的认知症发生率。通过结合非药物的主动干预，将帮助您更大程度避免认知症，保护您的脑健康！
♔Take away Today
01word&Phrases
Alzheimer's Disease related vocabularies
02
Sentence Context
P9⑥Given Americans’ apparent reluctance to get back to work { be it because of continued fears of infection with covid-19 generous unemployment insurance or both } wages may need to rise further.
03Reading tips
科技文章行文不晦涩，只是新的信息量被不熟悉领域的专业名词clogged导致flow不畅；解决方法一是用阅读技巧，以"我"为主进行阅读 二就是利用一篇文章为anchor，积累相关信息constructure来挂结性格信息peck
